Effects of neonatal dopamine depletion on sensory inhibition in the rat

Central dopamine systems appear to play an important role in sensory information processing. In particular, the filtering (or gating) of repetitive auditory stimuli is modulated by pharmacological manipulations that affect dopaminergic neurotransmission. The present study further addressed the role of dopamine in auditory gating. Three-day-old male Sprague-Dawley rats, pretreated with desipramine, received intracisternal injections of 6-hydroxydopamine (6-OHDA; 75 micrograms in 10 microliters) or the vehicle. At 4 months of age the rats were implanted for evoked potential recording and auditory gating was assessed using a paired click paradigm. Neonatally administered 6-OHDA did not alter gating in the adult rats. However, unlike for the control group, systemic amphetamine (1.83 mg/kg, IP) failed to disrupt gating in the treated rats. Apomorphine (1.0 mg/kg, SC) disrupted gating in both groups. Neonatal 6-OHDA treatment caused significant reductions in dopamine levels in the striatum, nucleus accumbens, and substantia nigra/ventral tegmental regions. There was an inverse relationship between substantia nigra/ ventral tegmental area dopamine levels and auditory gating. Overall, the results suggest that amphetamine-induced auditory gating loss requires presynaptic dopamine release, but that the deficiency occurs through postsynaptic dopamine receptor activation.